Coma Patients 'Talk' with Their Brains

by John Gever John Gever Deputy Managing Editor, MedPage Today
August 12, 2013

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Researchers said they established a primitive type of communication with two nonresponsive patients using fMRI to measure their attention to certain words, serving as responses to questions.

Note that the technique may be useful in establishing basic communication with patients who appear unresponsive to bedside examinations and cannot respond with existing neuroimaging methods, but further study is necessary.

Researchers said they established a primitive type of communication with two nonresponsive patients using functional MRI (fMRI) to measure their attention to certain words, serving as responses to questions.

Brain activity measured by fMRI in one patient with minimal consciousness and one in a persistent vegetative state demonstrated not only that they heard words spoken to them, but also could use their attention to the words to give "Yes" or "No" answers to questions about their names and location, according to Lorina Naci, PhD, and Adrian Owen, PhD, of Western University in London, Ontario.

The second patient, who had been in a persistent vegetative state for 12 years after a head injury, was able to "answer" in the negative when asked if he was in a supermarket, but affirmatively when asked if he was in a hospital. The patient also gave correct answers to yes-no questions about his name, the researchers reported online in JAMA Neurology.

These "answers" were in the form of increased activity in brain regions that had previously been activated during a training period in which patients were instructed either to count occurrences of the words "Yes" or "No" when spoken to them or to ignore them. Whether or not they counted accurately was not the point -- rather, it was to have them focus their attention on these words.

Then, when the patients were asked a Yes-No question, they were read a series of words that included "Yes" and "No" at different points. Patients' increased attention to either "Yes" or "No" during this exercise served as the response.

"To our knowledge, we show for the first time with functional magnetic resonance imaging that behaviorally nonresponsive patients can use selective auditory attention to convey their ability to follow commands and communicate," Naci and Owen wrote.

"The technique may be useful in establishing basic communication with patients who appear unresponsive to bedside examinations and cannot respond with existing neuroimaging methods," they added.

Other research groups had previously used imaging scans to show that some apparently comatose patients retain some cognitive ability despite being unable to move or speak. For example, in one study, fMRI showed distinctive patterns of brain activity when patients were told to imagine certain images. More recently, former Israeli Prime Minister Ariel Sharon, in a vegetative state for 6 years following a stroke, was found to show a unique pattern of brain activity in response to the voice of his son.

However, Naci and Owen pointed out, these studies have demonstrated awareness in only a small minority of patients examined. They wanted to explore other methods of establishing communication with nonresponsive patients that may work when these mental-imagery methods fail.

For the current study, the researchers first validated their training and testing approach in 15 healthy volunteers. They then tried it on three patients -- two in a minimally conscious state and one in a persistent vegetative state. However, the communication phase of the testing was not performed in one of the minimally conscious patients.

During the training phase, participants were read a total of 11 words -- the numbers one through nine, Yes, and No -- in no particular order. Participants were told that one word (Yes or No) was the target word and then were given the instruction "count," meaning that they should count every time they heard the target word. Then, in a subsequent session, they were again read a sequence of the 11 words but this time were told "relax" and pay no attention to the words. Participants underwent fMRI during these sessions to correlate brain activity patterns with the words as they were spoken.

The communication phase of the trial in the two patients was similar except that, instead of being told to "count" or "relax" during the word sequences, they were read a Yes-No question:

"Are you in a supermarket?"

"Are you in a hospital?"

"Is your name Steven?"

"Is your name Mike?"

"Is your name Scott?"

Patients were asked the two location questions and two of the name questions. When followed by the sequences of number-words, Yes, and No, "each patient could willfully choose which word to attend to (count) and which to ignore, depending on his answer to the specific question," Naci and Owen explained. The brain activity patterns established during the training phase would therefore allow the researchers to determine whether a patient was attending more to "Yes" than to "No," or vice versa.

For patient two, functional activation in two of four communication scans satisfied the region-of-interest analysis, the authors explained. For instance, when the question was "Is your name Steven?" the patient answered "Yes" by showing significantly more activity for Yes than No sequences in the prefrontal region of interest (T-score value=3.2, P<0.001).

Naci and Owen reported that all three patients showed more brain activity in response to the "count" instruction during the training phase, although the specific regions activated were different in each patient. This phase of the study "confirmed that [each patient] understood and followed the commands and was able to pay attention to some words while ignoring others that were irrelevant for the task."

Two separate editorials in JAMA Neurology lauded the researchers' efforts.

James Bernat, MD, of the Geisel School of Medicine at Dartmouth in Hanover, N.H., said the study had several important implications for patients.

He argued that it reinforces "the duty to treat [nonresponsive patients] as sentient persons," while also showing the importance of including fMRI into the diagnostic criteria for vegetative states.

Moreover, he wrote, the study "demonstrates the need to optimize" fMRI technologies for assessing cognitive ability in brain-damaged patients.

Kenneth M. Heilman, MD, of the University of Florida in Gainesville, also indicated that the study had the potential to be truly groundbreaking.

"The finding that [fMRI] may be used to communicate with patients who have a total locked-in syndrome may lead to a paradigmatic shift such that with the further development of prostheses, these unfortunate patients, as well as patients with other forms of locked-in syndromes, will be able to open the door to end their isolation," he wrote.

However, Alexander Khalessi, MD, MS, of the University of California San Diego, told MedPage Today in an interview that the study had some important limitations, and not only its very small sample size.

Noting that the three patients had different types of brain injuries, he suggested that it would be helpful in future studies to try the same approach in patients with a single type of injury.

"A better way going forward would be to take patients with ischemic stroke... because in those patients there is a well-defined anatomic deficit," he said. Such studies may then allow physicians to determine which types of structural damage correlate with cognitive function, which in turn may help guide rehabilitation.

Also, Khalessi said, "fMRI is ... a crude proxy for the physiology of the brain." He suggested that magnetoencephalography would be a better tool for measuring activity in specific brain regions.

The study was funded by the DECODER Project, the European Commission in the 7th Framework Programme, the James S. McDonnell Foundation, and the Canada Excellence Research Chairs Program.

The study authors and the two editorialists declared that they had no relevant financial interests.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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